Bromocriptine mesylate

RECENT MAJOR CHANGES Dosage and Administration, recommended evaluation before initiating bromocriptine mesylate (2.1) 06/2026 Dosage and Administration, dosage modification for strong and moderate CYP3A4 inhibitors (2.7) 06/2026 Contraindications, history of cardiac valvular disorders; pericardial fibrosis; pleural, pulmonary, or retroperitoneal fibrotic disorders (4, 5.1, 5.2) 06/2026 Warnings and Precautions (5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.8, 5.9) 06/2026

INDICATIONS AND USAGE Hyperprolactinemia-Associated Dysfunctions Bromocriptine mesylate tablets and capsules are indicated for the treatment of dysfunctions associated with hyperprolactinemia including amenorrhea with or without galactorrhea, infertility or hypogonadism . Bromocriptine treatment is indicated in patients with prolactin-secreting adenomas , which may be the basic underlying endocrinopathy contributing to the above clinical presentations. Reduction in tumor size has been demonstrated in both male and female patients with macroadenomas. In cases where adenectomy is elected, a course of bromocriptine therapy may be used to reduce the tumor mass prior to surgery. Acromegaly Bromocriptine mesylate tablet and capsule therapy is indicated in the treatment of acromegaly. Bromocriptine therapy, alone or as adjunctive therapy with pituitary irradiation or surgery, reduces serum growth hormone by 50% or more in approximately 1⁄2 of patients treated, although not usually to normal levels. Since the effects of external pituitary radiation may not become maximal for several years, adjunctive therapy with bromocriptine offers potential benefit before the effects of irradiation are manifested. Parkinson’s Disease Bromocriptine mesylate tablets or capsules are indicated in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson’s disease. As adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor), bromocriptine therapy may provide additional therapeutic benefits in those patients who are currently maintained on optimal dosages of levodopa, those who are beginning to deteriorate (develop tolerance) to levodopa therapy, and those who are experiencing “end of dose failure” on levodopa therapy. Bromocriptine therapy may permit a reduction of the maintenance dose of levodopa and, thus may ameliorate the occurrence and/or severity of adverse reactions associated with long-term levodopa therapy such as abnormal involuntary movements (e.g., dyskinesias) and the marked swings in motor function (“on-off” phenomenon). Continued efficacy of bromocriptine therapy during treatment of more than 2 years has not been established. Data are insufficient to evaluate potential benefit from treating newly diagnosed Parkinson’s disease with bromocriptine. Studies have shown, however, significantly more adverse reactions (notably nausea, hallucinations, confusion and hypotension) in bromocriptine-treated patients than in levodopa/carbidopa-treated patients. Patients unresponsive to levodopa are poor candidates for bromocriptine therapy.

2 DOSAGE AND ADMINISTRATION Before initiating bromocriptine mesylate capsules, evaluate for valvular heart disease, including with an echocardiogram. If valvular disease is detected, do not administer bromocriptine mesylate ( 2.1 ). Take bromocriptine mesylate capsules orally with food ( 2.2 ) Recommended dosage for hyperprolactinemia-associated dysfunction is 1.25 mg (one-half of a tablet) to 2.5 mg once daily. Increase the dosage up to 2.5 mg once daily every two to seven days within a recommended dosage of 2.5 mg to 15 mg once daily ( 2.3 ) Recommended dosage for prolactin-secreting adenomas is 1.25 mg to 2.5 mg once daily. Increase the dosage within a recommended dosage of 2.5 mg to 10 mg once daily ( 2.4 ) Recommended dosage for acromegaly is 1.25 mg to 2.5 mg once at bedtime for 3 days. Increase the dosage 1.25 mg to 2.5 mg once daily every 3 days to 7 days up to the maximum recommended dosage is 100 mg/daily ( 2.5 ). Recommended starting dosage for idiopathic or postencephalitic Parkinson's disease is 1.25 mg twice daily. Increase the dosage by 1.25 mg twice daily every 14 days to 28 days up to the maximum recommended daily dosage of 100 mg/day ( 2.6 ) For dosage modifications for concomitant use of bromocriptine mesylate with moderate CYP3A4 inhibitors, see Full Prescribing Information ( 2.7 , 7 ) 2.1 Recommended Evaluation Before Initiating bromocriptine mesylate Before initiating bromocriptine mesylate evaluate for valvular heart disease, including with an echocardiogram. If valvular disease is detected, do not administer bromocriptine mesylate [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . 2.2 Important Administration Instructions Take bromocriptine mesylate orally with food because a high percentage of patients vomited after they received bromocriptine mesylate under fasting conditions. 2.3 Recommended Dosage for Hyperprolactinemia-Associated Dysfunction The recommended starting dosage of bromocriptine mesylate in adults with hyperprolactinemia-associated dysfunction is 1.25 mg (one-half of a tablet) to 2.5 mg once daily. Increase the bromocriptine mesylate dosage up to 2.5 mg once daily every two to seven days as tolerated until an optimal therapeutic response is achieved within a recommended dosage of 2.5 mg to 15 mg once daily. 2.4 Recommended Dosage for Prolactin-Secreting Adenomas The recommended starting dosage of bromocriptine mesylate in adult and pediatric patients 11 years of age and older with prolactin-secreting adenomas is 1.25 mg (one-half of a tablet) to 2.5 mg once daily. Increase the bromocriptine mesylate dosage as tolerated until an optimal therapeutic response is achieved within a recommended dosage of 2.5 mg to 10 mg once daily. In cases where adenectomy is elected for prolactin-secreting adenomas, a course of bromocriptine mesylate therapy may be used to reduce the tumor mass prior to surgery. 2.5 Recommended Dosage for Acromegaly The recommended starting dosage of bromocriptine mesylate in adults for acromegaly is 1.25 mg (one-half of a tablet) to 2.5 mg once at bedtime for 3 days. Increase the dosage 1.25 mg to 2.5 mg once daily every 3 days to 7 days, as tolerated, until an optimal therapeutic response is achieved. Reevaluate patients monthly and modify the dosage based on growth hormone levels and clinical response. For adults with acromegaly, the usual optimal therapeutic dosage range varies from 20 mg to 30 mg once at bedtime in most patients, and the maximum recommended dosage is 100 mg/daily. After a brief trial with bromocriptine mesylate therapy in adults with acromegaly, if there is no significant reduction in growth hormone levels and no changes in the clinical features of acromegaly consider increasing the dosage or discontinuing bromocriptine mesylate. For patients with acromegaly treated with pituitary irradiation, withdraw bromocriptine mesylate (e.g., for four to eight weeks) on a yearly basis to assess the clinical effects of radiation on the disease pro …

3 DOSAGE FORMS & STRENGTHS Tablets: 2.5 mg of bromocriptine, off-white, round, flat-faced, beveled-edge tablets, debossed “E” above the score and “280” below the score on one side and debossed “2.5” on the other side. Capsules: 5 mg of bromocriptine, hard gelatin capsule size 3 with caramel opaque cap imprinted “102” on the cap and white opaque body, imprinted with “PARLODEL” over “5 mg” on the body. Tablets:2.5 mg of bromocriptine (functionally scored) (3) Capsules: 5 mg of bromocriptine (3)

CONTRAINDICATIONS Hypersensitivity to bromocriptine or to any of the excipients of bromocriptine mesylate capsules, uncontrolled hypertension and sensitivity to any ergot alkaloids. In patients being treated for hyperprolactinemia, bromocriptine mesylate tablets and capsules should be withdrawn when pregnancy is diagnosed (see PRECAUTIONS: Hyperprolactinemic States ). In the event that bromocriptine is reinstituted to control a rapidly expanding macroadenoma (see PRECAUTIONS: Hyperprolactinemic States ) and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing bromocriptine must be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. When bromocriptine is being used to treat acromegaly, prolactinoma, or Parkinson’s disease in patients who subsequently become pregnant, a decision should be made as to whether the therapy continues to be medically necessary or can be withdrawn. If it is continued, the drug should be withdrawn in those who may experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless withdrawal of bromocriptine is considered to be medically contraindicated. The drug should not be used during the postpartum period in women with a history of coronary artery disease and other severe cardiovascular conditions unless withdrawal is considered medically contraindicated. If the drug is used in the postpartum period, the patient should be observed with caution.

ADVERSE REACTIONS Adverse Reactions from Clinical Trials Hyperprolactinemic Indications The incidence of adverse effects is quite high (69%) but these are generally mild to moderate in degree. Therapy was discontinued in approximately 5% of patients because of adverse effects. These in decreasing order of frequency are: nausea (49%), headache (19%), dizziness (17%), fatigue (7%), lightheadedness (5%), vomiting (5%), abdominal cramps (4%), nasal congestion (3%), constipation (3%), diarrhea (3%) and drowsiness (3%). A slight hypotensive effect may accompany bromocriptine treatment. The occurrence of adverse reactions may be lessened by temporarily reducing dosage to 1⁄2 a bromocriptine mesylate tablet 2 or 3 times daily. A few cases of cerebrospinal fluid rhinorrhea have been reported in patients receiving bromocriptine for treatment of large prolactinomas. This has occurred rarely, usually only in patients who have received previous transsphenoidal surgery, pituitary radiation, or both, and who were receiving bromocriptine for tumor recurrence. It may also occur in previously untreated patients whose tumor extends into the sphenoid sinus. Acromegaly The most frequent adverse reactions encountered in acromegalic patients treated with bromocriptine were: nausea (18%), constipation (14%), postural/orthostatic hypotension (6%), anorexia (4%), dry mouth/nasal stuffiness (4%), indigestion/dyspepsia (4%), digital vasospasm (3%), drowsiness/tiredness (3%) and vomiting (2%). Less frequent adverse reactions (less than 2%) were: gastrointestinal bleeding, dizziness, exacerbation of Raynaud’s syndrome, headache and syncope. Rarely (less than 1%) hair loss, alcohol potentiation, faintness, lightheadedness, arrhythmia, ventricular tachycardia, decreased sleep requirement, visual hallucinations, lassitude, shortness of breath, bradycardia, vertigo, paresthesia, sluggishness, vasovagal attack, delusional psychosis, paranoia, insomnia, heavy headedness, reduced tolerance to cold, tingling of ears, facial pallor and muscle cramps have been reported. Parkinson’s Disease In clinical trials in which bromocriptine was administered with concomitant reduction in the dose of levodopa/carbidopa, the most common newly appearing adverse reactions were: nausea, abnormal involuntary movements, hallucinations, confusion, “on-off’’ phenomenon, dizziness, drowsiness, faintness/fainting, vomiting, asthenia, abdominal discomfort, visual disturbance, ataxia, insomnia, depression, hypotension, shortness of breath, constipation, and vertigo. Less common adverse reactions which may be encountered include: anorexia, anxiety, blepharospasm, dry mouth, dysphagia, edema of the feet and ankles, erythromelalgia, epileptiform seizure, fatigue, headache, lethargy, mottling of skin, nasal stuffiness, nervousness, nightmares, paresthesia, skin rash, urinary frequency, urinary incontinence, urinary retention, and rarely, signs and symptoms of ergotism such as tingling of fingers, cold feet, numbness, muscle cramps of feet and legs or exacerbation of Raynaud’s syndrome. Abnormalities in laboratory tests may include elevations in blood urea nitrogen, SGOT, SGPT, GGPT, CPK, alkaline phosphatase and uric acid, which are usually transient and not of clinical significance. Adverse Reactions from Postmarketing Experience The following adverse reactions have been reported during postapproval use of bromocriptine (All Indications Combined). Because adverse reactions from spontaneous reports are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Psychiatric Disorders: Confusion, psychomotor agitation/excitation, hallucinations, psychotic disorders, insomnia, libido increase, hypersexuality, and impulse control/compulsive behaviors (including gambling, spending, and other intense urges). Nervous System Disorders: Headache, drowsiness, dizziness, dyskinaesia, somno …

7 DRUG INTERACTIONS Alcohol Alcohol may potentiate bromocriptine mesylate -associated adverse reactions. Dopamine Antagonists The concomitant use of bromocriptine mesylate with dopamine antagonists resulted in a decreased efficacy of bromocriptine mesylate. Strong and Moderate CYP3A4 Inhibitors Avoid concomitant use of bromocriptine mesylate with strong CYP3A4 inhibitors. Follow the recommended bromocriptine mesylate dosage modifications during concomitant use with moderate CYP3A4 inhibitors [see Dosage and Administration ( 2.7 )]. Bromocriptine is a substrate of CYP3A4 [see Clinical Pharmacology ( 12.3 )] . Concomitant use with strong and moderate CYP3A4 inhibitors increases bromocriptine exposure [see Clinical Pharmacology ( 12.3 )], which may increase the risk of bromocriptine mesylate-associated adverse reactions. Ergot Alkaloids Concomitant use of bromocriptine mesylate with other ergot alkaloids is not recommended. If use is unavoidable, dosage reduction may be necessary in those cases where high dosages of bromocriptine mesylate are being used (such as patients with Parkinson's disease). Alcohol: Alcohol may potentiate bromocriptine mesylate adverse reactions ( 7 ). Dopamine Antagonists: Concomitant use of bromocriptine mesylate with dopamine antagonists: decreased efficacy of bromocriptine mesylate ( 7 ). Strong and Moderate CYP3A4 Inhibitors: Avoid concomitant use of bromocriptine mesylate with strong CYP3A4 inhibitors. Dosage modifications are recommended for bromocriptine mesylate when used with a concomitant moderate CYP3A4 inhibitor ( 7 ). Ergot Alkaloids: Concomitant use of bromocriptine mesylate with other ergot alkaloids is not recommended. If use is unavoidable, dosage reduction may be needed where high bromocriptine mesylate dosages are used ( 7 ).

8 USE IN SPECIFIC POPULATIONS Pregnancy: See the Full Prescribing Information regarding the recommendations for using bromocriptine mesylate during pregnancy ( 8.1 ) Lactation: Avoid the use of bromocriptine mesylate during lactation in postpartum females. ( 8.2 ). Females of Reproductive Potential: A pregnancy test is recommended in bromocriptine mesylate-treated patients at least every 4 weeks during the amenorrheic period. Advise females of reproductive potential not seeking pregnancy, or those harboring large adenomas, to use appropriate contraceptive measures during bromocriptine mesylate treatment ( 8.3 ). 8.1 Pregnancy Risk Summary Pregnancy in Patients with Hyperprolactinemia-Associated Dysfunction and Prolactin-Secreting Adenomas: In patients being treated with bromocriptine mesylate capsules for hyperprolactinemia, bromocriptine mesylate should generally be withdrawn when pregnancy is diagnosed. If bromocriptine mesylate is continued or reinstituted in select patients to manage a prolactin-secreting macroadenoma and a patient experiences a hypertensive disorder of pregnancy, the benefit of continuing bromocriptine mesylate capsules should be weighed against the possible risk of its use during a hypertensive disorder of pregnancy. Pregnancy in Patients with Acromegaly : In patients being treated with bromocriptine mesylate for acromegaly who subsequently become pregnant, a decision should be made as to whether bromocriptine mesylate continues to be medically necessary or can be withdrawn. Bromocriptine mesylate should be withdrawn in those who experience hypertensive disorders of pregnancy (including eclampsia, preeclampsia, or pregnancy-induced hypertension) unless bromocriptine mesylate use is necessary. Idiopathic Parkinson's Disease or Postencephalitic Parkinsonism: In patients being treated with bromocriptine mesylate for idiopathic Parkinson's disease or postencephalitic parkinsonism, there are no adequate data on the developmental risk associated with the use of the bromocriptine mesylate in pregnant women. If the decision is made to discontinue bromocriptine mesylate capsules, adverse reactions associated with rapid dosage reduction or withdrawal should be considered [see Warnings and Precatutions ( 5.11 )]. Risk of Major Birth Defects and Miscarriage: The estimated background risk of major birth defects and miscarriage in patients with hyperprolactinemia-associated dysfunctions, prolactin-secreting ademonas, acromegaly, or idiopathic Parkinson's disease or postencephalitic parkinsonism is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The incidence of birth defects in 1,109 live births was 3.3% in neonates/infants born to mothers who received bromocriptine mesylate capsules during pregnancy (see Data) . Clinical Considerations Maternal Adverse Reactions: Bromocriptine mesylate-treated patients should be monitored closely throughout pregnancy for signs and symptoms that may signal the enlargement of a previously undetected or existing prolactin-secreting tumor. Discontinuation of bromocriptine mesylate capsules treatment in patients with known macroadenomas has been associated with rapid regrowth of tumor and increase in serum prolactin in most cases. Prolactin-secreting adenomas may expand and compression of the optic or other cranial nerves may occur, emergency pituitary surgery becoming necessary. In most cases, the compression resolves following delivery. Reinitiation of bromocriptine mesylate capsules treatment has been reported to produce improvement in the visual fields of patients in whom nerve compression has occurred during pregnancy. Postpartum Period: Avoid use of bromocriptine mesylate capsules for the inhibition or suppression of postpartum physiologic lactation because of the ris …

12.1 Mechanism of Action Bromocriptine mesylate contains bromocriptine, an ergot derivative and dopamine receptor agonist, which activates post-synaptic dopamine receptors. Dopaminergic neurons in the tuberoinfundibular process release dopamine that modulates the secretion of prolactin from the anterior pituitary; in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Bromocriptine induces stereotyped behavior in rodents and turning behavior in rats (e.g., rats move in circles) that have unilateral lesions in the substantia nigra. These actions, characteristic of those produced by dopamine, are inhibited by dopamine antagonists and suggest a direct action of bromocriptine on striatal dopamine receptors. Bromocriptine inhibits the secretion of prolactin in humans, with little or no effect on other pituitary hormones, except in patients with acromegaly, where bromocriptine lowers elevated blood levels of growth hormone in the majority of patients. Bromocriptine produces its therapeutic effect in the treatment of idiopathic Parkinson's disease or postencephalitic parkinsonism, a clinical condition characterized by a progressive deficiency in dopamine synthesis in the substantia nigra, by directly stimulating the dopamine receptors in the corpus striatum.

11 DESCRIPTION Bromocriptine mesylate is an ergot derivative with potent dopamine receptor agonist activity. Bromocriptine mesylate is chemically designated as Ergotaman-3′, 6′, 18-trione, 2-bromo-12′­hydroxy-2′-(1-methylethyl)-5′-(2-methylpropyl)-, (5′α)-monomethanesulfonate (salt). The structural formula is: Complies with USP dissolution test 1. Bromocriptine mesylate tablets and Bromocriptine mesylate capsules are for oral administration. Bromocriptine mesylate tablets: Each tablet contains 2.5 mg of bromocriptine (equivalent to 2.87 mg of bromocriptine mesylate) and the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate [see Warnings and Precautions (5.9)], magnesium stearate, maleic acid, povidone and corn starch. Bromocriptine mesylate capsules: Each capsule contains 5 mg of bromocriptine (equivalent to 5.74 mg of bromocriptine mesylate) and the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate [see Warnings and Precautions (5.9)] , magnesium stearate, and maleic acid. The hard gelatin capsule contains gelatin, iron oxide red, titanium dioxide and purified water. The imprinting ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, propylene glycol and shellac. structure

OVERDOSAGE The most commonly reported signs and symptoms associated with acute bromocriptine overdose are: nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, malaise, confusion, lethargy, drowsiness, delusions, hallucinations, and repetitive yawning. The lethal dose has not been established and the drug has a very wide margin of safety. However, one death occurred in a patient who committed suicide with an unknown quantity of bromocriptine and chloroquine. Treatment of overdose consists of removal of the drug by emesis (if conscious), gastric lavage, activated charcoal, or saline catharsis. Careful supervision and recording of fluid intake and output is essential. Hypotension should be treated by placing the patient in the Trendelenburg position and administering I.V. fluids. If satisfactory relief of hypotension cannot be achieved by using the above measures to their fullest extent, vasopressors should be considered. There have been isolated reports of children who accidentally ingested bromocriptine. Vomiting, somnolence and fever were reported as adverse events. Patients recovered either spontaneously within a few hours or after appropriate management.

HOW SUPPLIED Bromocriptine Mesylate Capsules, USP are available containing bromocriptine mesylate, USP equivalent to 5 mg bromocriptine. The 5 mg capsules are hard-shell gelatin capsules with a light brown opaque cap and ivory opaque body filled with a white to off-white powder. The capsules are axially printed with MYLAN over 7096 in black ink on both the cap and body. They are available as follows: NDC 0378-7096-93 bottles of 30 capsules NDC 0378-7096-01 bottles of 100 capsules Store and Dispense: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Manufactured by: Granules India Limited Survey No. 160/A, 161/E, 162, 174/A, Gagillapur Village, Dundigal-Gandimaisamma Mandal, Medchal-Malkajgiri District – 500043, Telangana, INDIA AP/DRUGS/37/2003 Revised: 10/2021 GR:BROMC:R3